Various publications are referenced herein. These references, in their entireties, are hereby incorporated by reference into the subject application in order to more fully describe the state of the art to which the invention relates.
The field of cholinesterases has been recently reviewed by Taylor (J. Biol. Chem., 266:4025-4028 (1991)), which is hereby incorporated by reference into this application.
The classification of cholinesterases is based on the differential specificity of the enzyme for both substrate and inhibitors. Acetylcholinesterase (AChE, EC 3.1.1.7) is preferentially active with acetylcholine and is inhibited by BW-284C51 (Koelle, G.B. (1955) J. Pharmacol. Exp. Ther. 114:167-184; Holmstedt, B. (1957) Aota. Physiol. Scand. 40: 322-330; Holmstedt, B. (1959) Pharmacol. Rev. 567-688; Silver, A. (1973) in Cholinesterases, Academic Press; and Austin, L and Berry, W.K. (1953) Biochem. J. 54: 695-700).
Studies aimed at elucidating the function of acetylcholinesterase made use of a variety of inhibitors such as physostigmine (eserine). AChE inhibitors may be used to enhance the nicotinic and muscarinic actions of acetylcholine. Some cholinesterase inhibitors are the main ingredient of insecticides used against house pests or in agriculture. Cholinesterases may have use as prophylactic or therapeutic agents in cases of organophosphate poisoning. Acetylcholinesterase (AChE) is primarily associated with nerve and muscle, typically localized at synaptic contacts. AChE, an enzyme which degrades the esters of choline, emerged as a key component in neurotransmission within the autonomic and somatic motor nervous system (Dale, H.H. (1914) J. Pharmacol. Exp. Ther. 6:147-190.). Other cholinesterases e.g. butyrylcholinesterase (BuChE, EC 3.1.1.8) are located at other sites and have other physiological functions.